Childhood Obesity, Breastfeeding, Intestinal Microbiota, and Early Exposure to Antibiotics

Paolella, Gaetana; Vajro, Pietro

doi:10.1001/jamapediatrics.2016.0964

Cited by 19 publications

(18 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies on rifaximin, active on Gram-negative bacteria, show conflicting results in NASH patients ranging from a significant reduction of ALT, endotoxin and IL-10 levels [ 108 ] to the inefficacy on fat liver content and ALT levels [ 109 ]. Further studies on antibiotics as GLA-modulators are needed, especially to evaluate risks/benefits in light of recent data showing a possible increased risk of obesity due to antibiotic exposure in early life [ 104 , 110 ].…”

Section: Therapeutic Prospectivesmentioning

confidence: 99%

Gut–Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease

2017

Self Cite

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is the most frequent type of chronic liver disease in the pediatric age group, paralleling an obesity pandemic. A “multiple-hit” hypothesis has been invoked to explain its pathogenesis. The “first hit” is liver lipid accumulation in obese children with insulin resistance. In the absence of significant lifestyle modifications leading to weight loss and increased physical activity, other factors may act as “second hits” implicated in liver damage progression leading to more severe forms of inflammation and hepatic fibrosis. In this regard, the gut–liver axis (GLA) seems to play a central role. Principal players are the gut microbiota, its bacterial products, and the intestinal barrier. A derangement of GLA (namely, dysbiosis and altered intestinal permeability) may promote bacteria/bacterial product translocation into portal circulation, activation of inflammation via toll-like receptors signaling in hepatocytes, and progression from simple steatosis to non-alcoholic steato-hepatitis (NASH). Among other factors a relevant role has been attributed to the farnesoid X receptor, a nuclear transcriptional factor activated from bile acids chemically modified by gut microbiota (GM) enzymes. The individuation and elucidation of GLA derangement in NAFLD pathomechanisms is of interest at all ages and especially in pediatrics to identify new therapeutic approaches in patients recalcitrant to lifestyle changes. Specific targeting of gut microbiota via pre-/probiotic supplementation, feces transplantation, and farnesoid X receptor modulation appear promising.

show abstract

Section: Therapeutic Prospectivesmentioning

confidence: 99%

Gut–Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease

2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Gut microbiota ferment indigestible complex carbohydrates into short-chain fatty acids (including propionate, butyrate, and acetate) that can be readily used by the host colonocytes as an energy source [5] . Short-chain fatty acids and other microbial metabolites can also influence the secretion of gut-derived peptides, which consequently regulate gut motility, nutrient absorption, satiety, and energy homeostasis [29] . Finally, disturbance of gut microbiota can affect the integrity and function of the gut, resulting in translocation of lipopolysaccharides to the bloodstream and triggering low-grade inflammation, a condition that characterizes obesity and other metabolic disorders [29] .…”

Section: Infant Gut Microbiota and Obesitymentioning

confidence: 99%

Early-Life Antibiotic Exposure, Gut Microbiota Development, and Predisposition to Obesity

Azad¹,

Moossavi

Owora

et al. 2017

Intestinal Microbiome: Functional Aspects in Health and Disease

View full text Add to dashboard Cite

Antibiotics are often prescribed inappropriately to infants and young children, with potentially adverse effects on the developing gut microbiota and related metabolic processes. We review evidence from 17 epidemiologic studies suggesting that antibiotic exposure during critical periods of early development may influence weight gain and the development of obesity. Complementary research in both humans and rodents indicates that gut microbiota play a key role in this process, although further research is needed to confirm and characterize the causal mechanisms involved. Obesity is a complex and multifactorial condition; thus, a multipronged prevention strategy will be required to curb the current obesity epidemic. Evidence to date suggests this strategy should include the judicious use of antibiotics, especially in early life when the developing gut microbiota is particularly susceptible to perturbations with long-lasting implications for metabolic programming and obesity risk.

show abstract

“…Several lines of evidence indicate that specific gut microbiota may play a role in obesity, metabolic syndrome, and fatty liver by increasing energy harvesting in conditions of intestinal dysbiosis or small intestinal bacterial overgrowth (SIBO) [3,4]. In the presence of a damaged intestinal barrier (“leaky gut”), the gut-liver axis (GLA) may amplify he normal interactions between intestinal bacteria/bacterial products and hepatic receptors [5], thereby promoting a cascade of events, namely, oxidative stress, insulin-resistance (IR), hepatic inflammation and fibrosis, via a large number of metabolites [6].…”

Section: Introductionmentioning

confidence: 99%

Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations

et al. 2017

Self Cite

View full text Add to dashboard Cite

To get insight into still elusive pathomechanisms of pediatric obesity and non-alcoholic fatty liver disease (NAFLD) we explored the interplay among GC-MS studied urinary metabolomic signature, gut liver axis (GLA) abnormalities, and food preferences (Kid-Med). Intestinal permeability (IP), small intestinal bacterial overgrowth (SIBO), and homeostatic model assessment-insulin resistance were investigated in forty children (mean age 9.8 years) categorized as normal weight (NW) or obese (body mass index <85th or >95th percentile, respectively) ± ultrasonographic bright liver and hypertransaminasemia (NAFLD). SIBO was increased in all obese children (p = 0.0022), IP preferentially in those with NAFLD (p = 0.0002). The partial least-square discriminant analysis of urinary metabolome correctly allocated children based on their obesity, NAFLD, visceral fat, pathological IP and SIBO. Compared to NW, obese children had (1) higher levels of glucose/1-methylhistidine, the latter more markedly in NAFLD patients; and (2) lower levels of xylitol, phenyl acetic acid and hydroquinone, the latter especially in children without NAFLD. The metabolic pathways of BCAA and/or their metabolites correlated with excess of visceral fat centimeters (leucine/oxo-valerate), and more deranged IP and SIBO (valine metabolites). Urinary metabolome analysis contributes to define a metabolic fingerprint of pediatric obesity and related NAFLD, by identifying metabolic pathways/metabolites reflecting typical obesity dietary habits and GLA perturbations.

show abstract

Childhood Obesity, Breastfeeding, Intestinal Microbiota, and Early Exposure to Antibiotics

Cited by 19 publications

References 19 publications

Gut–Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease

Gut–Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease

Early-Life Antibiotic Exposure, Gut Microbiota Development, and Predisposition to Obesity

Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations

Contact Info

Product

Resources

About